NSAIDs Halt Damage in Spinal Arthritis

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Two papers provide supportive evidence that NSAIDs may slow the progression of bony change of the spine in ankylosing spondylitis.

Note that in these studies, patients with elevated markers of inflammation seemed to beneﬁt most from continuous treatment with NSAIDs.

The routine use of nonsteroidal anti-inflammatory drugs (NSAIDs) among patients with ankylosing spondylitis can slow the progression of bone changes in the spine, two groups of European researchers reported.

High NSAID use by patients with ankylosing spondylitis was associated with a significantly lower adjusted risk for progression of disease on radiographs (OR 0.15, 95% CI 0.02 to 0.96, P=0.045), according to Joachim Sieper, MD, of Charité Universitätsmedizin in Berlin, and colleagues.

In a second study which looked at continuous versus on-demand NSAID use, slowing of radiographic progression was most pronounced among patients with high levels of acute-phase reactants and when treatment was continuous rather than on-demand, according to Désirée van der Heijde, MD, of Leiden University Medical Center in Leiden, the Netherlands, and colleagues.

Both studies were published in the October Annals of the Rheumatic Diseases.

Treatment with NSAIDs is effective in symptomatic relief for patients with axial spondyloarthritis, and small studies have suggested that there also may be structural benefits.

To explore the possibility that these drugs might help prevent the debilitating spinal damage characteristic of ankylosing spondylitis and in the earlier stage nonradiographic axial spondyloarthritis, Sieper and colleagues analyzed data from the German Spondyloarthritis Inception Cohort.

Their analysis included 88 patients with radiographic ankylosing spondylitis and 76 with nonradiographic spondyloarthritis, comparing spinal x-ray findings at baseline and after 2 years.

The radiographs were graded for sacroiliitis according to the modified Stoke Ankylosing Spondylitis Spine Score system, with additional scores reflecting the presence or absence of the bony growths known as syndesmophytes.

NSAID intake was classified as low or high according to an index that reflects daily dosage and duration of use.

A total of 27.3% of patients with ankylosing spondylitis and 25% of those with nonradiographic spondyloarthritis were classified as high users.

High users tended to have worse scores on a disease activity index, worse functional impairment, higher baseline spine scores, and more syndesmophytes at baseline.

During 2 years of follow-up, the change in radiographic spine score for patients with ankylosing spondylitis was 0.02 units in high NSAID users compared with 0.96 in low users.

Moreover, fewer high users had definite progression as shown by worsening of their radiographic spine scores by 2 units or more (8.3% versus 21.9%).

That absolute change was not statistically significant, most likely because of small numbers and large differences in radiographic changes, but after adjustment for important factors such as baseline structural damage, the likelihood of slowing progression was significant (P=0.045).

The benefits of NSAID use were most prominent among patients at high risk for progression because of the presence of baseline syndesmophytes and high levels of acute-phase reactants.

For instance, among patients with syndesmophytes and high CRP, spine scores increased by 4.36 units compared with 0.14 units in those with low and high use of NSAIDs, respectively (P=0.02), the researchers found.

In contrast, patients with neither of those risk factors had very little progression, with changes in spine scores of only 0.35 and 0.07 units in the low and high NSAID groups, respectively.

These clear differences in the effects of high and low NSAID use among patients with ankylosing spondylitis were not seen in patients with nonradiographic spondyloarthitis, however (OR 0.60, 95% CI 0.06 to 6.61, P=0.679).

The inhibition of new bone formation observed among patients with ankylosing spondylitis in this study probably resulted from effects of COX2 on the synthesis of prostaglandins, which can stimulate bone growth, the researchers explained.

While concerns remain about the potential for cardiovascular and gastrointestinal adverse effects associated with long-term use of NSAIDs, the authors argued that their findings weigh in favor of the drugs' use in ankylosing spondylitis.

They also suggested that NSAIDs be evaluated in conjunction with tumor necrosis factor inhibitors, to see if combining the spinal benefits of NSAIDs with the anti-inflammatory effects of the biologic would further enhance outcomes.

The second study was a post-hoc analysis of a trial that compared continuous with on-demand use of NSAIDs among 150 patients with ankylosing spondylitis.

In that analysis, van der Heijde and colleagues performed a series of probability calculations that identified high levels of inflammation, as shown by elevated erythrocyte sedimentation rate, as an important predictor of structural damage.

They also determined in regression analyses that "continuous use of NSAIDs can almost completely counteract the negative influence of high ESR on structural damage."

In addition, because no statistical interaction was found for continuous use in patients with high versus low ESR (OR 0.57, 95% CI 0.11 to 3, P=0.566), they argued that "there seems to be an important role for a prostaglandin-mediated mechanism that is independent of the role of inflammation in the formation of syndesmophytes."

In an editorial that accompanied the two studies, Robert D. Inman, MD, of the University of Toronto, and colleagues, set out a personalized approach to the management of ankylosing spondylitis.

He emphasized these factors as being important in the decision to use NSAIDs:

The symptomatic status of of the patient

The patient's risk for radiographic progression

The risk for that patient of adverse effects from continuous treatment

Other available treatment options

"In the final analysis, treatment of [ankylosing spondylitis] must be customized to the individual patient," he stated.

The German Spondyloarthritis Inception Cohort has received funding from the German Federal Ministry of Education and Research, as well as from Abbott, Amgen, Centocor, Schering-Plough, and Wyeth.

The researchers in the both studies as well as the editorialist reported no financial conflicts.

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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